tbuckley/cabot-search huggingface dataset:
Scenarios of demographic distributional aspects of health co-benefits from decarbonising urban transport
Authors: Chenxi Lu, W Neil Adger, Karyn Morrissey, Shaohui Zhang, Sergey Venevsky, Hao Yin, Taochun Sun, Xuanren Song, Chao Wu, Xinyu Dou, Biqing Zhu, Zhu Liu
Journal: The Lancet Planetary Health (2022)

BackgroundThere is limited knowledge on the distribution of the health co-benefits of reduced air pollutants and carbon emissions in the transport sector across populations.MethodsThis Article describes a health impact assessment used to estimate the health co-benefits of alternative land passenger transport scenarios for the city of Beijing, China, testing the effect of five transport-based scenarios from 2020 to 2050 on health outcomes. New potential scenarios range from implementing a green transport infrastructure, to scenarios primarily based on the electrification of vehicle fleets and a deep decarbonisation scenario with near zero carbon emissions by 2050. The health co-benefits are disaggregated by age and sex and estimated in monetary terms.FindingsThe results show that all the alternative mitigation scenarios result in reduced PM2·5 and CO2 emissions compared to a business-as-usual scenario during 2020–50. The near zero scenario achieves the largest health co-benefits and economic benefits annually relative to the sole mitigation strategy, preventing 300 (95% CI 229–450) deaths, with health co-benefits and CO2 cost-saving an equivalent of 0·01% (0·00–0·03%) of Beijing's Gross domestic product in 2015 by 2050. Given Beijing's ageing population and higher mortality rate, individuals aged 50 years and older experience the greatest benefit from the mitigation scenarios. Regarding sex, the greatest health benefits occur in men.InterpretationThis assessment provides estimates of the demographic distribution of benefits from the effects of combinations of green transport and decarbonising vehicles in transport futures. The results show that there are substantial positive health outcomes from decarbonising transport in Beijing. Policies aimed at encouraging active travel and use of public transport, increasing the safety of active travel, improving public transport infrastructure, and decarbonising vehicles lead to differential benefits. In addition, disaggregation by age and sex shows that the health impacts related to transport pollution disproportionately influence different age cohorts and genders.FundingNational Natural Science Foundation of China and FRIEND Project (through the National Research Foundation of Korea, funded by the Ministry of Science and ICT).
Reply
Authors: Yong Lv, Guohong Han
Journal: Hepatology (2022)

We appreciate the interest of Luo and Yang in our recent study published in the Hepatology.[1] Firstly, we agree with Luo and Yang that there is currently a lack of consensus on the definition of spontaneous portosystemic shunt (SPSS). Nevertheless, gastroesophageal varices were generally excluded from the definition of SPSS in most recent studies.[2,3] Furthermore, our recent study showed that adding gastroesophageal varices embolization to transjugular intrahepatic portosystemic shunt (TIPS) did not decrease the risk of post‐TIPS over hepatic encephalopathy (HE) compared with TIPS alone,[4] whereas our other study suggested that large gastro‐paraesophageal shunts were associated with increased risk of post‐TIPS HE.[3] The location of varices and the type of shunts have been presented in Table 1 of the original study.[1] Due to the small sample size of the study, we did not perform further subgroup analysis. However, in the univariable and multivariable analysis, gastroesophageal varices and type of shunts were not associated with the incidence of HE after TIPS. In addition, all SPSS were identified and measured during TIPS angiography,[1] which had a better radiological visualization and more accurate quantification than cross‐sectional images (computed tomography or magnetic resonance imaging). Secondly, Luo and Yang suggested that balloon‐occluded retrograde transvenous obliteration (BRTO) may be better than coil embolization for achieving complete embolization of the SPSS. Indeed, a recent single‐center retrospective study showed that glue embolization of gastroesophageal varices during TIPS improves survival compared to coil‐only embolization.[5] Nevertheless, no liquid embolic material was used in our study, and a direct comparison to coil embolization was impossible. Thus, whether BRTO is superior to coil embolization of large SPSS during TIPS for the prevention of post‐TIPS HE in patients with cirrhosis merits further investigation. AUTHOR CONTRIBUTIONS Yong Lv and Guohong Han designed the letter; Yong Lv drafted the letter; Guohong Han revised the letter. CONFLICT OF INTEREST Nothing to report.
The compatibility of circularity and national dietary recommendations for animal products in five European countries: a modelling analysis on nutritional feasibility, climate impact, and land use
Authors: Anita Frehner, Renée P M Cardinaals, Imke J M de Boer, Adrian Muller, Christian Schader, Benjamin van Selm, Ollie van Hal, Giulia Pestoni, Sabine Rohrmann, Mario Herrero, Hannah H E van Zanten
Journal: The Lancet Planetary Health (2022)

<h2>Summary</h2><h3>Background</h3> National food-based dietary guidelines (FBDGs) are generally designed from a human health perspective and often disregard sustainability aspects. Circular food production systems are a promising solution to achieve sustainable healthy diets. In such systems, closing nutrient cycles where possible and minimising external inputs contribute to reducing environmental impacts. This change could be made by limiting livestock feed to available low-opportunity-cost biomass (LOCB). We examined the compatibility of national dietary guidelines for animal products with livestock production on the basis of the feed supplied by available LOCB. <h3>Methods</h3> We investigated whether the national dietary recommendations for animal products for Bulgaria, Malta, the Netherlands, Sweden, and Switzerland could be met with domestically available LOCB. We used an optimisation model that allocates feed resources to different species of farm animals. Of the resulting scenarios, we assessed the nutritional feasibility, climate impact, and land use. <h3>Findings</h3> Our results showed the environmental benefits of reducing the recommended animal products in the FBDGs, and that animal products from LOCB could provide between 22% (Netherlands) and 47% (Switzerland) of total protein contributions of the FBDGs. This range covers a substantial part of the nutritional needs of the studied populations. To fully meet these needs, consumption of plant-based food could be increased. <h3>Interpretation</h3> Our results contribute to the discussion of what quantities of animal products in dietary guidelines are compatible with circular food systems. Thus, national dietary recommendations for animal products should be revised and recommended quantities lowered. This finding is consistent with recent efforts to include sustainability criteria in dietary guidelines. <h3>Funding</h3> Swiss National Science Foundation and the Dutch Research Council.
A Case of Infective Endocarditis Associated With Patent Ductus Arteriosus in Which PET/CT Was Useful for Diagnosis
Authors: Taiju Miyagami, Seiko Kushiro, Mari Arikawa, Koji Murakami, Toshio Naito
Journal: Clinical Nuclear Medicine (2022)

Abstract A 33-year-old woman presented to our hospital with a 4-month history of fever of unknown origin. Physical examination revealed a vascular murmur in the left subclavian region. Blood culture revealed bacteria and PET/CT revealed tracer accumulation in the patent ductus arteriosus area, leading to the diagnosis of infective endocarditis in this area. This case report may aid in diagnosing this disease in the future, as infective endocarditis in a patent ductus arteriosus is rare and difficult to diagnose.
Sodium-calcium exchanger-3 regulates pain “wind-up”: From human psychophysics to spinal mechanisms
Authors: Teodora Trendafilova, Kaustubh Adhikari, Annina B. Schmid, Ryan Patel, Erika Polgár, Kim I. Chisholm, Steven J. Middleton, Kieran Boyle, Allen C. Dickie, Evangelia Semizoglou, Jimena Perez-Sanchez, Andrew M. Bell, Luis Miguel Ramirez-Aristeguieta, Samar Khoury, Aleksandar Ivanov, Hendrik Wildner, Eleanor Ferris, Juan-Camilo Chacón-Duque, Sophie Sokolow, Mohamed A. Saad Boghdady, André Herchuelz, Pierre Faux, Giovanni Poletti, Carla Gallo, Francisco Rothhammer, Gabriel Bedoya, Hanns Ulrich Zeilhofer, Luda Diatchenko, Stephen B. McMahon, Andrew J. Todd, Anthony H. Dickenson, Andres Ruiz-Linares, David L. Bennett
Journal: Neuron (2022)

Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is "wind-up," in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up in healthy human volunteers and found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was expressed in mouse dorsal horn neurons, and mice lacking NCX3 showed normal, acute pain but hypersensitivity to the second phase of the formalin test and chronic constriction injury. Dorsal horn neurons lacking NCX3 showed increased intracellular calcium following repetitive stimulation, slowed calcium clearance, and increased wind-up. Moreover, virally mediated enhanced spinal expression of NCX3 reduced central sensitization. Our study highlights Ca
Oncologic outcomes of patients with lymph node–positive Merkel cell carcinoma with unknown primary: A retrospective cohort study
Authors: Jane Yuet Ching Hui, Saranya Prathibha, McKenzie White, Corinne E. Praska, Christopher J. LaRocca, Jacob Ankeny, Evidio Domingo-Musibay, Lori Fiessinger, Eric H. Jensen, Todd M. Tuttle, Schelomo Marmor
Journal: Journal of the American Academy of Dermatology (2022)
Intrinsically Bioactive Manganese–Eumelanin Nanocomposites Mediated Antioxidation and Anti‐Neuroinflammation for Targeted Theranostics of Traumatic Brain Injury
Authors: Duo Sun, Kaijun Liu, Yang Li, Tian Xie, Mi Zhang, Yu Liu, Haipeng Tong, Yu Guo, Qianhui Zhang, Heng Liu, Jingqin Fang, Xiao Chen
Journal: Advanced Healthcare Materials (2022)

Overproduced reactive oxygen species and the induced oxidative stress and neuroinflammation often result in secondary injury, which is associated with unfavorable prognosis in traumatic brain injury (TBI). Unfortunately, current medications cannot effectively ameliorate the secondary injury at traumatic sites. Here, it is reported that intrinsically bioactive multifunctional nanocomposites (ANG-MnEMNPs-Cur, AMEC) mediate antioxidation and anti-neuroinflammation for targeted TBI theranostics, which are engineered by loading the neuroprotective agent curcumin on angiopep-2 functionalized and manganese doped eumelanin-like nanoparticles. After intravenous delivery, efficient AMEC accumulation is observed in lesions of TBI mice models established by controlled cortical impact method, evidenced by T1 -T2 magnetic resonance and photoacoustic dual-modal imaging. Therapeutically, AMEC effectively alleviates neuroinflammation, protects blood-brain barrier integrity, relieves brain edema, reduces brain tissue loss, and improves the cognition of TBI mice. Mechanistically, following the penetration into the traumatic tissues via angiopep-2 mediated targeting effect, the efficacy of AMEC is synergistically improved by combined functional moieties of curcumin and eumelanin. This is achieved by the alleviation of oxidative stress, inhibition of neuroinflammation via M1-to-M2 macrophage reprogramming, and promotion of neuronal regeneration. The as-developed AMEC with well-defined mechanisms of action may represent a promising targeted theranostics strategy for TBI and other neuroinflammation-associated intracranial diseases.
Contact lenses for pravastatin delivery to eye segments: Design and in vitro-in vivo correlations
Authors: Ana F. Pereira-da-Mota, Maria Vivero-Lopez, Maria Serramito, Luis Diaz-Gomez, Ana Paula Serro, Gonzalo Carracedo, Fernando Huete-Toral, Angel Concheiro, Carmen Alvarez-Lorenzo
Journal: Journal of Controlled Release (2022)

Oral administration of cholesterol-lowering statins, HMG-CoA reductase inhibitors, is associated with beneficial effects on eye conditions. This work aims to design contact lenses (CLs) that can sustainedly deliver pravastatin and thus improve the ocular efficacy while avoiding systemic side effects of statins. Bioinspired hydrogels were prepared with monomers that resemble hydrophobic (ethylene glycol phenyl ether methacrylate) and amino (2-aminoethyl methacrylamide hydrochloride) functionalities of the active site of HMG-CoA. Best performing CLs loaded >6 mg/g, in vitro fulfilled the release demands for daily wearing, and showed anti-inflammatory activity (lowering TNF-α). High hydrostatic pressure sterilization preserved the stability of both the drug and the hydrogel network. Ex vivo tests revealed the ability of pravastatin to accumulate in cornea and sclera and to penetrate through transscleral route. In vivo tests (rabbits) confirmed that, compared to eye drops and for the same dose, CLs provided significantly higher pravastatin levels in tear fluid within 1 to 7 h of wearing. Moreover, after 8 h wearing pravastatin was present in cornea, sclera, aqueous humour and vitreous humour. Strong correlations between percentages of drug released in vitro and in vivo were found. Effects of volume and proteins on release rate and Levy plots were identified.
Projected Impact of the Medicare Part D Senior Savings Model on Diabetes-Related Health and Economic Outcomes Among Insulin Users Covered by Medicare
Authors: Hui Shao, Dawei Guan, Jingchuan Guo, Tianze Jiao, Yongkang Zhang, Jing Luo, Lizheng Shi, Vivian Fonseca, Joshua D. Brown
Journal: Diabetes Care (2022)

OBJECTIVE The Medicare Part D Senior Savings Model (SSM) took effect on 1 January 2021. In this study we estimated the number of beneficiaries who would benefit from SSM and the long-term health and economic consequences of implementing this new policy. RESEARCH DESIGN AND METHODS Data for Medicare beneficiaries with diabetes treated with insulin were extracted from the 2018 Medical Expenditure Panel Survey. A validated diabetes microsimulation model estimated health and economic impacts of the new policy for the 5-year initial implementation period and a 20-year extended policy horizon. Costs were estimated from a health system perspective. RESULTS Of 4.2 million eligible Medicare beneficiaries, 1.6 million (38.3%) would benefit from the policy, and out-of-pocket (OOP) costs per year per beneficiary would decrease by 61% or $500 on average. Compared with non-White subgroups, the White population subgroups would have a higher proportion of SSM enrollees (29.6% vs. 43.7%) and a higher annual OOP cost reduction (reduction of $424 vs. $531). Among the SSM enrollees, one-third (605,125) were predicted to have improved insulin adherence due to lower cost sharing and improved health outcomes. In 5 years, the SSM would 1) avert 2,014 strokes, 935 heart attacks, 315 heart failure cases, and 344 end-stage renal disease cases; 2) gain 3,220 life-years and 3,381 quality-adjusted life-years (QALY); and 3) increase insulin cost and total medical cost by $3.5 billion and $2.8 billion. In 20 years, the number of avoided clinical outcomes, number of life-years and QALY gained, and the total and insulin cost would be larger. CONCLUSIONS The Medicare SSM may reduce the OOP costs for approximately one-third of the Medicare beneficiaries treated with insulin, improving health outcomes via increased insulin adherence. However, the SSM will also increase overall Medicare spending for insulin and overall medical costs, which may impact future premiums and benefits. Our findings can inform policy makers about the potential impact of the new Medicare SSM.
LTBK-04. LATE BREAKING ABSTRACT: MEK162 (binimetinib) in children with progressive or recurrent low-grade glioma: a multi-institutional phase II and target validation study
Authors: Nathan Robison, Jasmine Pauly, Jemily Malvar, Sharon Gardner, Jeffrey Allen, Ashley Margol, Tobey MacDonald, Anne Bendel, Lindsay Kilburn, Andrew Cluster, Daniel Bowers, Kathleen Dorris, Nicole Ullrich, Rebecca Loret De Mola, Elizabeth Alva, Sarah Leary, Patricia Baxter, Ziad Khatib, Kenneth Cohen, Tom Belle Davidson, Ashley Plant, Pratiti Bandopadhayay, Sylwia Stopka, Nathalie Agar, Karen Wright, Marvin Nelson, Yueh-Yun Chi, Mark Kieran
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND RAS/RAF/MEK/ERK pathway activation is the primary driver for most pediatric low-grade gliomas (pLGG). MEK162 (binimetinib) is an orally bioavailable MEK1/2 inhibitor with superior brain penetration in a preclinical model. The primary objective of this multi-institutional phase II and target validation study was to assess stratum-specific efficacy of binimetinib in progressive pLGG. METHODS Eligible children aged 1-18 years with previously treated radiographically progressive pLGG were enrolled and treated with binimetinib, starting dose 32mg/m2/dose twice daily. Stratum 1 included patients with pLGG with documented BRAF fusion; stratum 2, neurofibromatosis 1 (NF1)-associated pLGG; stratum 3, sporadic pLGG without documented BRAF fusion; and stratum 4, patients undergoing planned tumor biopsy who began binimetinib preoperatively. Partial and minor responses (PR and MR) were defined as ≥50% and ≥25% decrease in maximal two-dimensional measurements. RESULTS Of 86 patients enrolled, 85 were evaluable for response. Of these, 48 (56%) showed a radiographic response (30 PR and 18 MR) in the first year of treatment. Response rate for stratum 1 (n=28) was 50% (12 PR and 2 MR); 12 (43%) had stable disease (SD) and 2 (7%) progressive disease (PD). Stratum 2 (n=21) response rate was 43% (5 PR, 4 MR), with 12 (57%) SD and no PD. Stratum 3 (n=29) response rate was 69% (10 PR, 10 MR), 4 (14%) SD and 5 (17%) PD. Stratum 4 (n=7) include 3 PR, 2 MR, 2 SD. Nineteen (22%) discontinued treatment for toxicity (most commonly dermatologic), and an additional 42 (49%) required dose reduction. Median dose at the time of PR/MR was 28mg/m2; responses were seen at doses as low 16mg/m2. CONCLUSION Binimetinib is highly effective in the treatment of both NF1-associated and sporadic pLGG, with or without documented BRAF fusion. Modified dosing strategies to improve tolerability may be considered in future trials.
Brain Structure Among Middle-aged and Older Adults With Long-standing Type 1 Diabetes in the DCCT/EDIC Study
Authors: Alan M. Jacobson, Barbara H. Braffett, Guray Erus, Christopher M. Ryan, Geert J. Biessels, José A. Luchsinger, Ionut Bebu, Rose A. Gubitosi-Klug, Lisa Desiderio, Gayle M. Lorenzi, Victoria R. Trapani, John M. Lachin, R. Nick Bryan, Mohamad Habes, Ilya M. Nasrallah
Journal: Diabetes Care (2022)

Individuals with type 1 diabetes mellitus (T1DM) are living to ages when neuropathological changes are increasingly evident. We hypothesized that middle-aged and older adults with long-standing T1DM will show abnormal brain structure in comparison with control subjects without diabetes.
Identification of antimalarial targets of chloroquine by a combined deconvolution strategy of ABPP and MS-CETSA
Authors: Peng Gao, Yan-Qing Liu, Wei Xiao, Fei Xia, Jia-Yun Chen, Li-Wei Gu, Fan Yang, Liu-Hai Zheng, Jun-Zhe Zhang, Qian Zhang, Zhi-Jie Li, Yu-Qing Meng, Yong-Ping Zhu, Huan Tang, Qiao-Li Shi, Qiu-Yan Guo, Ying Zhang, Cheng-Chao Xu, Ling-Yun Dai, Ji-Gang Wang
Journal: Military Medical Research (2022)

Abstract Background Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine (CQ) has played an indispensable role, however, its mechanism of action (MoA) is not fully understood. Methods We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling (ABPP) and mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays. Results We developed a novel clickable, photo-affinity chloroquine analog probe (CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photo-crosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods. Conclusions We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled (ABPP) and label-free (MS-CETSA) methods.
Oral antiviral treatment in patients with systemic rheumatic disease at risk for development of severe COVID-19: a case series
Authors: George E Fragoulis, Christos Koutsianas, Kalliopi Fragiadaki, Ilias Mariolis, Stylianos Panopoulos, Christina Tsalapaki, Maria Pappa, Theodoros Dimitroulas, Maria G Tektonidou, Dimitrios Vassilopoulos, Petros P Sfikakis
Journal: Annals of the Rheumatic Diseases (2022)
Increasing diversity in genomics requires investment in equitable partnerships and capacity building
Authors: Alicia R. Martin, Rocky E. Stroud, Tamrat Abebe, Dickens Akena, Melkam Alemayehu, Lukoye Atwoli, Sinéad B. Chapman, Katelyn Flowers, Bizu Gelaye, Stella Gichuru, Symon M. Kariuki, Sam Kinyanjui, Kristina J. Korte, Nastassja Koen, Karestan C. Koenen, Charles R. J. C. Newton, Ana Maria Olivares, Sam Pollock, Kristianna Post, Ilina Singh, Dan J. Stein, Solomon Teferra, Zukiswa Zingela, Lori B. Chibnik
Journal: Nature Genetics (2022)